Chiral Oleﬁns as Ligands for Asymmetric Catalysis · Chiral Oleﬁns as Ligands for Asymmetric...

Chiral Olefins as Ligands for Asymmetric Catalysis

Hui-Wen Shih

Group Meeting

April 20, 2011

Johnson, J. B.; Rovis, T. Angew. Chem., Int. Ed. 2008, 47, 840.

Defieber, C.; Grutzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482.

M

A Brief History

! 1827: Zeise reports first metal-olefin complex

! 1962: Cope prepares the first chiral olefin

Pt ClCl

Cl

H HH H

Zeise's salt

K

Pt

fractionalcrystallization

racemicCl

Cl

NH

H

H

H

H

PhMe

PtCl

Cl

NH

PhMe

Zeise, W. C. Poggendorffs Ann. Phys. 1827, 9, 632.Cope, A. C.; Howell, C. F.; Knowles, A. J. Am. Chem. Soc. 1962, 84, 3191.

A Brief History

! 2003: Field begins to accelerate with Hayashi's report of chiral diene ligands in rhodium catalysis

! 1981: Hosokawa and Murahashi develop catalytic asymmetric reaction with chiral allyl ligand

R

O

R1

R2B(OH)2Bn

Bn3.2 mol%

1.5 mol% [RhCl(C2H4)2]2R

O

R1R2

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11509.Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318.

OH

Me

MeMe Pd

OAc

2

Cu(OAc)2, O2, MeOH O

Metal-Olefin Binding

! Dewar!Chatt!Duncanson model

! Comparison of ligand binding energies, "Eint

M M

# donation $ back-donation

Metal-olefin bond strength is determined by $ back-bonding

Back-donation increases with metal principle quantum number

HAu L HAu* L*! "Eint

HAu

H

H

H

H

HAu

H

H

HAu C O HAu PMe

MeMe HAu

HN

CNH

HAu NMe

MeMe

27.626.6 34.2 43.8 52.729.9


Metal-Olefin Binding

! Olefins have large preparation energies for binding


XnM L XnM L*! "Eint "Eprep

L*

double bond elongationsp2 to sp3 rehybridization

"Eprep

! Factors that affect binding strength

strain release

substituent electronics

entropy

sterics

OO OCN Ph n-Bu

CO2Me

CO2Me

> >>

> >>

>

Tolman, C. A. J. Am. Chem. Soc. 1974, 96, 2780.Hartley, F. R. Chem. Rev. 1973, 73, 163.

Classes of Chiral Olefins

M

M P M N

M

!-allyl diene

phosphane-olefin amine-olefin

Chiral Allyl Ligands

! 1981: First catalytic asymmetric reaction (Hosokawa and Murahashi, Osaka University)

OH

Me

MeMe Pd

OAc

2

Cu(OAc)2, O2 or t-Bu-OOH O

64% Y, 18% ee

Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318.

O

37% Y, 26% ee

O

63% Y, 21% ee

O

65% Y, 6% ee

O

71% Y, 1% ee

MeO Me Cl MeOC

Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282.

MeOH

16% Y, 22% ee 28% Y, 18% ee 47% Y, 5% ee 38% Y, 0.1% ee

43% Y, 17% ee



OH

Me

MeMe Pd

OAc

2


64% Y, 18% ee

Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318.Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282.

MeOH43% Y, 17% ee

Me Me

PdMe

HO

H

OMe

LPdII

LPd-H

LPd-OH

OH

Me

MeMe Pd

OAc

2



OH

Me

MeMe Pd

OAc

2


64% Y, 18% ee

Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318.Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282.

MeOH43% Y, 17% ee

Me Me

PdMe

HO

H

Me sits in space under C-1 bridgeheadolefin is trans to ligand

attack occurs from back facePhenyl blocks space under C-1

no enantioselectivity

Phenoxy coordinationgenerates opposite enantiomer

Me Me

1

Ph

Me Me

PdMe H

1O

Modified catalyst


! Yamamoto: Pd-allyl complexes for enantioselective allylation

THF or DMF, 0 oC

Nakamura, H.; Nakamura, K.; Yamamoto., Y. J. Am. Chem. Soc. 1998, 120, 4242.

R H

NR1

Me

PdCl

2

5 mol%SnBu3

R

HNR1

Ph

HNBn

62% Y, 81% ee

Ph

HNPr

c-hex

HNBn

62% Y, 70% ee 64% Y, 40% ee

Ph

HNPh

74% Y, 0% ee

X

Fernandes, R. A.; Yamamoto. Y. J. Org. Chem. 2004, 69, 3562.

Ph

HNBn

81% Y, 82% ee

2-Nap

HNBn

HNBn

69% Y, 88% ee 77% Y, 69% ee

c-hex

HNBn

63% Y, 60% ee

CO2Me CO2Me CO2Me CO2Me

S

X



H2O, THF, 0 oC

Fernandes, R. A.; Yamamoto., Y. J. Am. Chem. Soc. 2003, 125, 14133.

R H

NR1

Me

PdCl

2

5 mol%SnBu3

R

HNR1

Ph

HNBn

86% Y, 85% ee 63% Y, 18% ee 77% Y, 7% ee

c-hex

HNBn

84% Y, 50% ee

NH

NH

Ph

HNBn

86% Y, 91% ee

Ph

HN

4-pyr

HNBn

83% Y, 84% ee 98% Y, 67% ee

c-hex

HNBn

86% Y, 52% ee

Fernandes, R. A.; Yamamoto. Y. J. Am. Chem. Soc. 2004, 69, 735.

SiMe3

TBAF



H2O, THF, 0 oC

Fernandes, R. A.; Yamamoto., Y. J. Am. Chem. Soc. 2003, 125, 14133.

R H

NR1

Me

PdCl

2

5 mol%SnBu3

R

HNR1

SiMe3

TBAF

Me Me

PdMe

N R

HBn

Me Me

PdMe

NBn

R

Htrans-imine

favored disfavored

cis-imine

Me Me

PdMe

N H

RBn

Me Me

PdMe

NBn

H

R

no stereochemicalbias


M

M P M N

M

!-allyl diene


Chiral Diene Ligands

! Classes of Chiral Diene Ligands

Ph

Ph

FF

F

F

H

H

Ar

Ar

Me

Me

O

O

Traunertetrahydropentalenes

Xu, Lin, Laschat

R

R

R

R

R

R

nbd bodbnd bdd

cod

tfbHayashi

Me OMe

Carreira

MsHN NHMs

Du

Ar

ArDu

Me OMe

Me

Me

R1

R

Carreira

Ph

codGrützmacherHayashi

Hayashi Hayashi HayashiHayashi

Rhodium-Catalyzed 1,4-Additions

! Hayashi's Seminal Publication

O

Bn

Bn3.2 mol%

1.5 mol% [RhCl(C2H4)2]2

O

PhKOH, dioxanes/H2O, 30 oC 94% Y, 96% ee

O

4-OMeC6H4

89% Y, 95% ee

O

4-CF3C6H4

90% Y, 99% ee

O

73% Y, 88% ee

n-C5H11

O

2-Np

96% Y, 96% ee

O

Ph

O

Ph

Me

O

Ph i-Pr

i-PrO

O

Ph i-Pr

88% Y, 88% ee 81% Y, 97% ee 73% Y, 92% ee81% Y, 90% ee

Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.

PhB(OH)2


! Hiyashi's Seminal Publication

O

Bn

Bn3.2 mol%

1.5 mol% [RhCl(C2H4)2]2

O

PhKOH, dioxanes/H2O, 30 oC 94% Y, 96% ee


! Norbornadiene ligands are C2-symmetric

Ph

Ph

Rh PhRh

Bn

BnPh

O

favored

Rh

Bn

BnPh

O

disfavored

O

O

Ph

O

Ph

higher catalytic activity

better reactivity

compared to phosphine ligands

PhB(OH)2


! Catalytic cycle

Kina, A.; Yasuhara, Y.; Nishimura, T.; Iwamura, H.; Hayashi, T. Chem. Asian J. 2006, 1, 707.

[Rh]HO

[Rh]OH

[Rh]OHsol

[Rh]Phsol

PhB(OH)2

B(OH)3

O

O

Ph

transmetallationinsertion/hydrolysis

H2O

Kdimer = 3.8 x 102 M-1

K1 = 6.7 M-1s-1K1 = 16 M-1s-1

ratedet.step

catalyst resting state

[Rh(OH)(cod)]2catalyst


! Comparison of reaction kinetics: diene vs. phosphine ligand

Kina, A.; Yasuhara, Y.; Nishimura, T.; Iwamura, H.; Hayashi, T. Chem. Asian J. 2006, 1, 707.

[Rh]HO

[Rh]OH

[Rh]OHsol

Kdimer = 3.8 x 102 M-1 K1 = 6.7 M-1s-1 K2 = 16 M-1s-1

catalyst resting state

[Rh(OH)(cod)]2

active catalyst

[Rh]Phsol

transmetallation[Rh]

OHsol

insertion/

[Rh(OH)(binap)]2 Kdimer = 8 x 102 M-1 K1 = 0.5 M-1s-1

[Rh(OH)(cod)]2 is 20 times more reactive

[Rh(OH)(cod)]2

equilibrium content of active catalyst is higher

transmetallation occurs faster

Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052.

hydrolysis

Rhodium-Catalyzed 1,4-Additions: Catalyst Loading

! Catalyst loading can be decreased significantly

Chen, F.-X.; Kina, A.; Hayashi, T. Org. Lett. 2006, 8, 341.

O

1.5 mol% [RhCl(C2H4)2]2

O

PhBenchmark

Bn

Bn

(S,S)-Bn-bod)

catalyst (mol% Rh) yield (%) ee (%)PhB(OH)2

3.3 mol%

PhB(OH)2 1.0 quant 96

PhB(OH)2 0.1 quant 96

PhB(OH)2 0.05 79 96

PhB(OH)2 0.01 0 --

(PhBO)3 0.01 quant 96

(PhBO)3 0.005 71 96

impurity in boronic acid deactivates catalyst

PhB(OH)2


! Carreira independently reports Rh-catalyzed 1,4 addition with C1-symmetric ligand

Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. Org. Lett. 2004, 6, 3873.

O

3.3 mol%

1.5 mol% [RhCl(C2H4)2]2

O

Ph

KOH, dioxanes/H2O, 25 oC 87% Y, 95% ee

Me OMe

MeMe

Me

PhB(OH)2

O

4-OMeC6H4

85% Y, 96% ee

O

4-COMeC6H4

96% Y, 97% ee

O

Ph

O

Ph

91% Y, 94% ee 81% Y, 95% ee

O O

Ph

Me

O Me

Ph Ph2N

O Ph

Me MeO

O Ph

Me

43% Y, 98% ee 68% Y, 89% ee 98% Y, 93% ee 93% Y, 88% ee


! Carreira independently reports Rh-catalyzed 1,4 addition with C1-symmetric ligand

Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. Org. Lett. 2004, 6, 3873.

O

3.3 mol%

1.5 mol% [RhCl(C2H4)2]2

O

Ph


Me OMe

MeMe

Me

PhB(OH)2

Me OMe

Me

t-Bu

! Ligand modification gives insight in catalyst binding

52% Y, 71% ee

Me OMe

Me

93% Y, 58% ee

Me OMe

Me

< 10% conversion

Me OMe

MeMe

Me

87% Y, 95% ee

Rigid diene structure required for activity

Rhodium-Catalyzed 1,4-Additions: Ligand Development

! Fumaric compounds are amenable to transformation

Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett. 2004, 6, 3425.

1.5 mol% [RhCl(C2H4)2]2KOH, dioxanes/H2O, 50 oC 90% Y, 90% ee

PhB(OH)2

3.2 mol% MesMes

t-BuO

OOt-Bu t-BuO

OOt-Bu

Ph

O O

! Diene ligands are more selective than traditional ligands

PPh2

PPh2

96% Y, 21% ee

PPh2

PPh2

99% Y, 3% ee

O

O

O

O

N

N

PPh2

PPh2

94% Y, 13% ee

MeOMeO

OMe

OMe

O

OP NEt2

50% Y, 32% ee(R)-binap (R)-segphos (S)-P-phos (S)-phosphoramidite

Rhodium-Catalyzed 1,4-Additions: Expansion of Scope

! Malemide compounds are amenable to transformation

Shintani, R.; Duan, W.-L.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 5628.

1.5 mol% [RhCl(C2H4)2]2KOH, dioxanes/H2O, 50 oC

77-95% Y, 82-92% ee

ArB(OH)2

3.2 mol% MesMes

! Diene ligands and phosphine ligand display orthogonal reactivity

N

O

O

Cy N

O

O

CyAr

1.25 mol% [RhCl(C2H4)2]2PhB(OH)2N

O

O

Bn N

O

O

CyArEtEt

2.75 mol% ligandN

O

O

Cy

Et

Ph

(R)-Binap

Ph

Ph

85% 15%

10% 84%

Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett. 2004, 6, 3425.


! Benchmark reaction: Phenyl boronic acid 1,4-addition to cyclohexenone


! Hayashi's C2-symmetric ligands

90% Y, 95% ee 89% Y, 97% ee

O

1.5 mol% [RhCl(C2H4)2]2

O

Ph

3 mol% diene ligand

Bn

Bn

Ph

Ph

97% Y, 95% ee

Bn

Bn

not stable to air/light stable

98% Y, 90% ee93% Y, 83% ee

Ph

Ph

Ph

Ph

Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673.

PhB(OH)2



! Hayashi's state of the art ligand

O

1.5 mol% [RhCl(C2H4)2]2

O

Ph

3 mol% diene ligand

Nishimura, T.; Nagaosa, M.; Hayashi, T. Chem. Lett. 2008, 37, 860.

FF

F

F

R

R

98% Y, 99% ee

R = (!)-mentholpre-catalyst

Ligand can be synthesized in 3 steps

High reactivity

High selectivity

PhB(OH)2



! Prochiral ligands

O

1.5 mol% [RhCl(C2H4)2]2

O

Ph

3 mol% diene ligand

Kina, A.; Ueyama, K.; Hayashi, T. Org. Lett. 2005, 7, 5889.

R

RR S

Ph

92% Y, 62% ee

Grützmacher

cyclooctatetraene

R

RR S

cyclooctadiaene

R

R

Ph

90% Y, 43% ee

Hayashi

ligand dissociatesand racemizes

Using PhZnCl (fast) 89% Y, 81% ee

Ph

Läng, F.; Breher, F.; Stein, D.; Grützmacher, H. Organometallics 2005, 24, 2997.

PhB(OH)2



! Other ligands under development

O

1.5 mol% [RhCl(C2H4)2]2

O

Ph

3 mol% diene ligand

Feng, C.-G.; Wang, Z.-Q.; Tian, P.; Xu, M.-H.; Lin, G.-Q. Chem. Asian J. 2008, 3, 1511.

95% Y, 88% ee

Laschat96% Y, 95% ee

Du

Wang, Y.; Hu, X.; Du, H. Org. Lett. 2010, 12, 5482.

H

H Ph

Ph

96% Y, 91% ee

Xu and Lin

Easy to synthesize

Norbornadiene mimics

NHMsMsHN

Binding occurs through olefin

Complex has fast coordination/dissociation

Helbig, S.; Sauer, S.; Cramer, N.; Laschat, S.; Baro, A.; Frey, W. Adv. Synth. Catal. 2007, 349, 2331.

TsN n-Bu

Me

89% Y, 91% ee

Yu

Li, Q.; Dong, Z.; Yu, Z.-X.; Org. Lett. 2011, 13, 1122.

Obtained from Rh allylic C-H

activation/conjugated diene addn

PhB(OH)2


! 1,4-Addition into aldehydes

! 1,4-Addition into cinnamaldehydes

1.5 mol% [RhCl(C2H4)2]2

3.3 mol%

Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 10850.Hayashi, T.; Tokunaga, N.; Okamoto, K.; Shintani, R. Chem. Lett. 2005, 34, 1480.

Fessard, T. C.; Andrews, S. P.; Motoyoshi, H.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 9331.

H

O

RBn

Bn

ArB(OH)2 H

O

R

Ar

R = alkyl, arylAr = e! rich, neutral, e! poor

1.5 mol% [RhCl(C2H4)2]2

3.3 mol%

H

O

Ar1 Ar2B(OH)2 H

O

Ar2

Ar1

83-95% Y, 88-97% ee

MeO Me

Me i-Bu

Bn

Ar1,2 = e! rich, neutral, e! poor63-90% Y, 89-93% ee

H

O

Ph4-MeOC6H4B(OH)2

1.5 mol% [RhCl(diene]2

then [{Rh(cod)Cl}2], dpppOMe

CH3

71% Y, 93% ee

! 1,1-Diarylethanes via one-pot addition/decarbonylation


! 1,4-Addition into esters

! 1,4-Addition into Weinreb amides

1.5 mol% [RhCl(C2H4)2]2

3.3 mol%

Paquin, J.-F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett. 2005, 7, 3821.Shintani, R.; Kimura, T.; Hayashi, T. Chem. Comm. 2005, 3213.

Shintani, R.; Okamoto, K. Hayashi, T. Org. Lett. 2005, 7, 4757.

t-BuO

O

Ar1

Bn

Bn

Ar2B(OH)2 t-BuO

O

Ar1

Ar2

Ar1,2 = e! rich, neutral, e! poor

1.5 mol% [RhCl(C2H4)2]2

3.3 mol%

N

O

R ArB(OH)2 N

O

R

Ar

62-95% Y, 89-93% ee

MeO Me

Me i-Bu

Bn

Ar = e! rich, neutral

83-92% Y, 80-92% ee

RO

O

SiMe2PhArB(OH)2

89-96% Y, 93-99% ee

! 1,4-Addition into "-silyl carbonyls

Ar1 includes heteroaromatics

Me

OMe OMe

Me

R = alkyl, aryl

RO

O

SiMe2Ph

Ar3.3 mol%

Bn

Bn

1.5 mol% [RhCl(C2H4)2]2

Ar = e! rich, neutral, e! poorR = alkyl, aryl


! 1,4-Addition into N-phthalimides

! 1,4-Addition to form quaternary centers

Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.; Hayashi, T. J. Am. Chem. Soc. 2009, 131, 13588.Nishimura, T.; Tokuji, S.; Sawano, T.; Hayashi, T. Org. Lett. 2009, 11, 3222.

Nishimura, T.; Wang, J. Nagaosa, M.; Okamoto, K.; Shintani, R.; Kwong, F.-Y.; Yu, W.-Y. Chan, A. S. C.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 464.

Ar4BNa

Ar = e! rich, neutral

83-92% Y, 80-92% ee

RO

O

NPhthArB(OH)2

81-99% Y, 93-99% ee

! 1,4-Alkynylation of cyclic enones

linear and cyclic carbonyls

RO

O

NPhth

Ar

1.5 mol% [RhCl(diene*)2]2

diene*=

FF

F

F

R

R

R = 2,6-dimethylphenylAr = e! rich, neutral, e! poor, vinyl

O

R


diene*=

Me

O-2Np

OMe

Me O

RPh

R = Me, Et, CO2Me

O

Si SiiPr3

HO

i-Pri-Pr 5 mol% [RhCl(C2H4)2]2

6 mol%

Bn

Bn O

SiiPr391% Y, 86% ee


! Seminal publication: Hayashi, 2004

! Scope


Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.

H

NTs

Cl

(PhBO)3Ph

HNTs

Cl

96% Y, 98% ee

Ph

Phdiene* =

Ph

HNTs

F3C

97% Y, 95% ee

Ph

HNTs

MeO

96% Y, 99% ee

Ph

HNTs

Me2N

94% Y, 98% ee

HNTs

99% Y, 99% ee

HNTs

97% Y, 96% ee

Ph

HNTs

99% Y, 99% ee

O

OMeCl

HNTs

96% Y, 99% ee

Me

challenging with phosphine ligandsbenchmark reaction


! Seminal publication: Hayashi, 2004

! Stereochemical model


Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.

H

NTs

Cl

(PhBO)3Ph

HNTs

Cl

96% Y, 98% ee

Bn

Bndiene* =

challenging with phosphine ligandsbenchmark reaction

Ph

Ph

Rh Ph

N

Rh

Ph

PhPh

favored disfavored

ArH

Ts

NTs

H

ArRh

Ph

PhPhN

Ar

H

Ts

Ph

HNTs

Cl

Ph

HNTs

Cl

High enantioselectivity

results from Ts and Ar inunsubstituted quadrants


! Benchmark reaction: 1,2 Ts- and Ns-imine addition

! Ligand development and survey


Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673.

H

NR

Cl

(PhBO)3Ph

HNR

Cl

88% Y, 94% ee95% Y, 99% ee

Ph

Ph

Ph

Ph

R = Ts, Ns R = Ts, Ns

Ts

Ns

99% Y, 90% ee96% Y, 98% ee

Ph

Ph

Ph

Ph

Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.

Ph

Ph

96% Y, 99% ee

Ph

Ph

92% Y, 99% ee

Bn

Bn

98% Y, 92% ee

Bn

Bn

88% Y, 81% ee

Me

O-2,6(Me)2Ar

OMe

Me

Me

O-2,6(Me)2Ar

OMe

Me

98% Y, 98% ee

96% Y, 99% ee

Otomaru, Y.; Hayashi, T.; Rawal, V. H. Chem. Comm. 2009, 4815.



! Ligand effects on rate: electron deficient ligand (1a) accelerates transmetallation


Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673.

H

NR

Cl

(PhBO)3Ph

HNR

Cl

5: 95% Y, 99% ee

Ph

Ph


Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.

Ph

Ph

3a: 96% Y, 99% ee

Bn

Bn

3b: 98% Y, 92% ee Me

O-2,6(Me)2Ar

OMe

Me

1a: 98% Y, 98% ee

Otomaru, Y.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009, 4815.



! Ligand development and survey


Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336.

H

NR

Cl

(PhBO)3Ph

HNR

Cl


Wang, L.; Wang, Z.-Q.; Xu, M.-H.; Lin, G.-Q. Synthesis 2010, 3263.

81% Y, 99% ee

94% Y, 99% ee

Cao, Z.; Du, H. Org. Lett. 2010, 12, 2602.

OMe

OMe

H

H

Ph

Ph

H

H

Ph

Ph

Ts

Ns

Lin

Du

OMe

HNSO2NMe2

82% Y, 84% ee


! 1,2-Addition into aldehydes


Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun. 2009, 5713.

H

O

(PhBO)3Ph

OH

95% Y, 86% ee

FF

F

F

Fc

Fcdiene* =

Ph

OH

99% Y, 78% ee

! Reaction scope

Ph

OH

85% Y, 78% ee

Ph

OH

99% Y, 85% eeMe Br

OMe

Ferrocenyl Ph

OH

94% Y, 85% ee

2-OMeC6H4

OH

97% Y, 85% ee

4-MeC6H4

OH

90% Y, 85% ee

2-ClC6H4

OH

91% Y, 86% ee

Mes

OH

87% Y, 94% ee

Carborhodation with Chiral Diene Ligands

! Rhodium-catalyzed addition/cyclization

! Catalytic cycle

Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.

Bn

Bn

MeBnO

BnOO

H

7.5 mol%

3.5 mol% [RhCl(C2H4)2]2KOH, dioxanes/H2O

BnO

BnO Ph

Me

OH

PhB(OH)2

60 oC 89% Y, 94% ee

[Rh]-OH

[Rh]-Ph

BnO

BnOO

PhMe

[Rh]

BnO

BnO Ph

Me

O[Rh]

PhB(OH)2

B(OH)3

MeBnO

BnOO

H

H2O

product

transmetallationhydrolysis

cyclization addition


! Rhodium-catalyzed addition/cyclization into alkynes

! Rhodium-catalyzed addition/cyclization into alkenes

Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34, 1416.

Bn

Bn5 mol%


35 oC 97% Y, 81% ee

Me

R

R=C(Me)(CO2Me)2

O

H

B(OH)2Me

OH

R

83% Y, 93% ee

O

H

BF3K

OH

5 mol% [IrCl(coe)2]2

FF

F

F

Ph3SiO

10 mol%

OSiPh3

n-hex n-hex

Et3N, PhMe/H2O, 60 oC

Nishimura, T.; Yasuhara, Y.; Nagaosa, M.; Hayashi, T. Tetrahedron: Asymmetry 2008, 17, 1778.



! Rh/diene catalysts favor alkyne arylation over 1,4-addition

Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew. Chem. Int. Ed. 2005, 44, 3909.

Bn

Bn

EtMeO2C

MeO2C

7.5 mol%


MeO2C

MeO2C

Ph

Et

PhB(OH)2

60 oC 93% Y, 99% ee

CO2Me CO2Me

MeMeO2C

MeO2CCO2Me

Et

Me

MeO2C

MeO2C

[Rh] PhB(OH)2

MeMeO2C

MeO2CCO2Me

Ph

Me

MeO2C

MeO2C

PhEt

[Rh] PhB(OH)2

Binap 76% < 3% (rec SM)cod 81% 80%



! Rh/diene catalysts favor alkyne arylation over 1,4-addition

Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew. Chem. Int. Ed. 2005, 44, 3909.

Bn

Bn

EtMeO2C

MeO2C

7.5 mol%


MeO2C

MeO2C

Ph

Et

PhB(OH)2

60 oC 93% Y, 99% ee

CO2Me CO2Me

MeMeO2C

MeO2CCO2Me

Et

Me

MeO2C

MeO2C

[Rh] PhB(OH)2

MeMeO2C

MeO2CCO2Me

Ph

Me

MeO2C

MeO2C

PhEt

cod 7% 76%


! Rhodium-catalyzed [4+2]

! Catalytic cycle

Shintani, R.; Sannohe, Y.; Tsuji, T; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.

Ph

Ph

PhMeO2C

MeO2C

diene* =

2.5 mol% [RhCl(diene*)2]2AgSbF6, CH2Cl2, 25 oC

MeO2C

MeO2C

87% Y, 94% ee

Me

Ph

H

Me

product

coordinationreductive elimination

1,3 allyl migration

PhMeO2C

MeO2C Me

PhMeO2C

MeO2C MeRhI

[RhI]

MeO2C

MeO2CRhIII

H

Ph

Me

MeO2C

MeO2CH

RhIII

Me

Ph

oxidative cyclization


! Rhodium-catalyzed cyclopropanation

! Rh/diene catalyst

Nishimura, T.; Maeda, Y.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, 7324.

2 mol% [RhCl(diene*)2]2

NaBARF4, PhMe, 40 oC

86% Y, 89% ee

Ph MeO OMeN2

O O

Ph

MeO2C CO2Me

FF

F

F

ONi-Pr2

i-Pr2N O

RhCl

Chiral Dienes in Resolutions

! Carreira's seminal publication: kinetic resolution of allyl carbonates

1.5 mol% [IrCl(COE)2]2

Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. J. Am. Chem. Soc. 2004, 126, 1628.

! Resolution of BIPHEP

Me OMe

Me

t-Bu

3.6 mol%

R

OCO2Me

R

OCO2Me

R

OPh

0.5 equiv PhOH28-46% Y, 80-98% ee

PPh2

PPh2

racemizes at room temp[RhCl(diene*)2]2

MeO Me

Me

t-Bu

diene* =

Me

MeO Ar

PP

Rh

PhPh

PhPhMe

Me

OH

57% Y, 12% eehydroboration of

styrene

Faller, J. W.; Wilt, J. C. J. Organomet. Chem. 2006, 691, 2207.

Chiral Dienes in Suzuki!Miyaura Coupling

! First enantioselective reaction employing Pd-diene catalyst

! Scope

Zhang, S.-S.; Wang, Z.-Q.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2010, 12, 5546.

MeBr B(OH)2

Ph

Ph H

H

diene* =

5 mol% Pd(diene*)Cl215 mol% diene*

Cs2CO3, PhMe, rt

Me

78% Y, 90% ee

Me

90% Y, 84% ee

Me CHO

90% Y, 73% ee

MeO

BnO Me

93% Y, 65% ee

MeO

PMBO Me

83% Y, 65% ee

Me

72% Y, 48% ee

Me


M

M P M N

M

!-allyl diene


Chiral Phosphane-Olefin Ligands

! Hybrid ligands combine advantages of phosphanes and olefins

M Pgood chiral environmentabout metal

strong coordination ability

! Classes of chiral phosphane-olefin ligands

R

PPh2

Hayashi

PPh2

Grützmacher

PPhPh

Widhalm

O

OP N

Carreira

PPh2ReOC COOC

Bolm

O

O

Me

Me

PPh2

Du

OEt

Ph2PO

OTr

Boysen

PPh2Fe

Stepnicka


! Phosphane-olefin ligands also participate in 1,4-additions

! Reactivity is similar to diene ligand

O ligand =

[RhCl(ligand)]3 (5 mol% Rh)

O

Ph


PPh2

Ph

transmetallationinsertion/hydrolysisratedet.step

[Rh]OHsol

[Rh]Phsol

PhB(OH)2

B(OH)3

O

O

Ph

H2O

[Rh] trimer

Duan, W.-L.; Iwamura, H.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 2130.

[Rh(OH)(cod)]2

catalyst

PhB(OH)2


Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849.Kasak, P.; Arion, V. B.; Widhalm, M. Tetrahedron: Asymmetry 2006, 17, 3084.

! Wilhalm's ligand improves reactivity/selectivity

O

0.5 mol% [RhCl(ligand)]2

O

Ph

KOH, dioxanes/H2O, 50 oC88% Y, 98% ee

P Ph

Ph

! Tropp ligands are versatile

O

5 mol% [Rh(OH)2(ligand)2]

O

Ph

KOH, dioxanes/H2O, 50 oC> 85% conv, 95% ee

Ph2P

Ph

PhB(OH)2

PhB(OH)2


Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849.Maire, P.; Deblon, S.; Breher, F.; Geier, J.; Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H. Chem. Eur. J. 2004, 10, 4198.

! Hemilability of tropp ligand facilitates hydrogenation

! Olefin hydrogenation

0.01 mol% [Ir(ligand)2]OTfH2, CH2Cl2 > 85% conv, 60% ee

Ph2P

Ph

Ph Me

NPh

Ph2P

Omenthol

[Ir(tropp)(cod)]OTf, H2Ph Me

NHPh

> 98% Y, 86% ee

MeO

O

OMeO

MeO

O

OMeO

Me


Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849.Maire, P.; Deblon, S.; Breher, F.; Geier, J.; Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H. Chem. Eur. J. 2004, 10, 4198.

! Hemilability of tropp ligand facilitates hydrogenation

P PIr

P

PIr

HH

3 H2

P

PIr

HHX

Y

P

PIr

L

L

L

L

Y

XH2

pre-catalyst is bound to P and olefin

hydrogenation is reversible

tropp ligand is hydrogenated in active catalyst


Liu, Z.; Du, H. Org. Lett. 2010, 12, 3054.

Shintani, R.; Duan, W.-L.; Okamoto, K.; Hayashi, T. Tetrahderon: Asymmetry 2005, 16, 3400.

! Pd-allyl chemistry is now also possible

Ph Ph

OAc

MeO OMe

OO [PdCl(allyl)]2

Ph Ph

CO2MeMeO2C

O

O

Me

Me

PPh2

98% Y, 95% ee

PPh2

87% Y, 96% ee

Ph

PPh2FeOEt

Ph2PO

OTrPh

Ph

90% Y, 61% ee100% Y, 43% ee

Kasak, P.; Arion, W. B.; Widhalm, M. Tetrahedron: Asymmetry 2006, 17, 3084.Minuth, T.; Boysen, M. M. K. Org. Lett. 2009, 11, 4212.


! Carreira demonstrates allylic amination with Ir/P-olefin system

! Stereoretentive allylic amination

3 mol% [IrCl(coe)2]2DMF, rt

Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 3139.

O

OP N

6 mol%

OH

H3NSO3

NH3Cl

70% Y, 70% ee

R

OHH3NSO3 R

NH3Cl

46-70% Y, 74-98% enantio-retention

conditions

see above

Roggen, M.; Carreira, E. M. J. Am. Chem. Soc. 2010, 132, 11917.


! Carreira demonstrates allylic amination with Ir/P-olefin system

Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 3139.

Roggen, M.; Carreira, E. M. J. Am. Chem. Soc. 2010, 132, 11917.

N

HO

MeMe

N

HO

MeMe

SO3

R

OH

R

O H

NMeMe

IrI

RIrIII

NH3

R

NH3HSO4


M

M P M N

M

!-allyl diene


Chiral Amine-Olefin Ligands

! Ligand lability is a challenge

Ph

NH HN

Ph

NH

Bn

CO2Me

NH HN

HN

tropp

N

! Unlike phosphane ligands, less prone to oxidation

! Based on phosphanyl-dibenzo-cycloheptene (tropp) framework

Maire, P.; Breher, F.; Schönberg, H.; Grützmacher, H. Organometallics 2005, 24, 3207.

Grützmacher, H.; Büttner, T.; Maire, P.; Ramseier, M.; Scheschkewitz, D.; Zweifel, T. DE 102004027771, 2006; EP 05011539.3

Vogt, M.; de Bruin, B.; Berke, H.; Trincado, M.; Grützmacher, H. Chem. Sci. 2011, 2, 723.


! Single example of asymmetric catalysis - Transfer hydrogenation

Me

O

Me

OH

>98% conv, 82% ee

IrN

NCO

Cl

Ph

Ph

(S,S)-[IrCl(CO)(trop2dpen)]

1 mol% Ir catalyst

10 mol% KOtBui-PrOH, 80 oC, 1h

H

H

Ir is bound to both N1 and N2 and C=Ctropp

Ir!C=Ctropp =1.968 Å

C=Ctropp = 1.501 Å



! Single example of asymmetric catalysis - Transfer hydrogenation

Me

O

Me

OH

>98% conv, 82% ee

IrN

NCO

Cl

Ph

Ph

(S,S)-[IrCl(CO)(trop2dpen)]

1 mol% Ir catalyst

10 mol% KOtBui-PrOH, 80 oC, 1h

H

H


IrCl(CO)(trop2dpen)KOtBu

Ir(CO)(trop2dpen-H)i-PrOH

IrH(CO)(trop2dpen)

Me

O

C=O H-bond to NHIr-H is equatorial

Final Thoughts

! Young and acelerating field

! Ligand classes:

M

diene

MR2P

MR2N


! Late transition metals: Pd, Rh, Ir

! Reaction types:

A

O

R

A

O

RR'

H

X

R R'

X

R

R

EWG

R

Ar

EWG

1,4

1,2

carbo-

rhodationCycloaddition

R R

H HChiral Resolution

H2

! Advantages: novel/improved reactivity, low catalyst loading, mild conditions, chiral about metal

! Disadvantages: field is still at start of development, ligand synthesis challenging

R R

Chiral Oleﬁns as Ligands for Asymmetric Catalysis · Chiral Oleﬁns as Ligands for Asymmetric...

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